Universal and Expanded Screening Strategy for Congenital Cytomegalovirus Infection: Is Pool Testing by a Rapid Molecular Test in Saliva a New Choice in Developing Countries?

BACKGROUND: Several screening strategies for identifying congenital CMV (cCMV) have been proposed; however, the optimal solution has yet to be determined. We aimed to determine the prevalence of cCMV by universal screening with saliva pool testing and to identify the clinical variables associated with a higher risk of cCMV to optimize an expanded screening strategy. METHODS: We carried out a prospective universal cCMV screening (September/2022 to August/2023) of 2186 newborns, analyzing saliva samples in pools of five (Alethia-LAMP-CMV®) and then performed confirmatory urine CMV RT-PCR. Infants with risk factors (small for gestational age, failed hearing screening, HIV-exposed, born to immunosuppressed mothers, or <1000 g birth weight) underwent expanded screening. Multivariate analyses were used to assess the association with maternal/neonatal variables. RESULTS: We identified 10 infants with cCMV (prevalence: 0.46%, 95% CI 0.22-0.84), with significantly higher rates (2.1%, 95% CI 0.58-5.3) in the high-risk group (p = 0.04). False positives occurred in 0.09% of cases. No significant differences in maternal/neonatal characteristics were observed, except for a higher prevalence among infants born to non-Chilean mothers (p = 0.034), notably those born to Haitian mothers (1.5%, 95% CI 0.31-4.34), who had higher odds of cCMV (OR 6.82, 95% CI 1.23-37.9, p = 0.04). Incorporating maternal nationality improved predictive accuracy (AUC: 0.65 to 0.83). CONCLUSIONS: For low-prevalence diseases such as cCMV, universal screening with pool testing in saliva represents an optimal and cost-effective approach to enhance diagnosis in asymptomatic patients. An expanded screening strategy considering maternal nationality could be beneficial in resource-limited settings.

Optimizing congenital cytomegalovirus detection by pool testing in saliva by a rapid molecular test.

Universal congenital cytomegalovirus (cCMV) screening in saliva is increasingly recommended. The aim of our study was to correlate the performance of a point-of-care rapid molecular test with CMV real time PCR (CMV RT-PCR) detection, using saliva pool-testing in newborns under a universal screening strategy. Saliva swabs were prospectively collected from newborns < 21 days old and tested by Alethia-LAMP-CMV assay in pools of 5 samples. In positive pools, subjects were tested individually and by saliva and urine CMV RT-PCR. A subset of negative pools were studied with both techniques and viral loads in whole blood were determined in positive patients. From 1,642 newborns included in 328 pools, 8 were confirmed by urine CMV RT-PCR, (cCMV prevalence 0,49%). The PPA and NNA of the pooled saliva Alethia-LAMP-CMV testing were 87,5% and 99,8% with a negative and positive predictive value of 99,9% and 77,7%, respectively. Two false positives were detected (0,12%). A subset of 17 negative pools (85 samples), studied by saliva CMV RT-PCR, showed 100% concordance.  Conclusion: CMV pool-testing using a rapid molecular test in saliva proved feasible when compared to PCR gold standards. This strategy could improve cost-effectiveness for cCMV universal neonatal screening, based on the low prevalence of the infection and could be a more affordable approach in less developed regions with reduced detection capacity. What is Known: • cCMV is the most frequent congenital infection and a leading nongenetic cause of sensorineural hearing loss and brain disease. • Universal screening could allow early detection of congenitally infected infants, improving clinical outcome. • Saliva PCR is the preferred and non-invasive test for newborn cCMV screening. What is New: • The feasibility of a universal cCMV screening by pool-testing in saliva using a rapid test in pools of 5 samples. • PPA and NPA were 87,5 and 99,8% compared to CMV PCR in urine. • This strategy could be relevant specially in LMIC where detection capacity is reduced and could improve cost-effectiveness. • cCMV prevalence in our center was 0,49%.

[Histoplasma capsulatum: an emerging agent in Chile?] / Histoplasma capsulatum: ¿un agente emergente para Chile?

In the last eleven months, we have diagnosed 9 cases of Histoplasmosis in our country. All patients affected were from endemic areas of South-America. Here, we wish to inform and prevent to all clinical laboratories from Chile about the presence of Histoplasma capsulatum in clinical samples. In the same way we want to prepare and raising awareness of the strengthening of biosecurity measures.

Histoplasma capsulatum: ¿un agente emergente para Chile? / Histoplasma capsulatum: an emerging agent in Chile?

Resumen En los últimos 11 meses, nuestro laboratorio ha diagnosticado 9 casos de histoplasmosis de presentación clínica en el territorio nacional. Todos los pacientes asociados a los cuadros clínicos son inmigrantes. Por medio del presente trabajo deseamos difundir y alertar a los profesionales de los laboratorios clínicos de nuestro país de la presencia y circulación de cepas de Histoplasma capsulatum en muestras clínicas. Asimismo, deseamos concientizar en el reforzamiento de las medidas de bioseguridad al interior de los laboratorios clínicos.

In the last eleven months, we have diagnosed 9 cases of Histoplasmosis in our country. All patients affected were from endemic areas of South-America. Here, we wish to inform and prevent to all clinical laboratories from Chile about the presence of Histoplasma capsulatum in clinical samples. In the same way we want to prepare and raising awareness of the strengthening of biosecurity measures.

Primary Budd-Chiari syndrome: outcome of endovascular management for suprahepatic venous obstruction.

OBJECTIVE: Primary Budd-Chiari syndrome (BCS) is a rare form of hepatic venous outflow obstruction at the suprahepatic inferior vena cava (IVC), the hepatic veins, or both. We assessed our 4-year experience in the management of BCS to evaluate the results of our methods of care. METHODS: We conducted a retrospective review of a nonrandomized clinical trial conducted in three teaching hospitals. Among 28 primary BCS patients, 9 remained in medical treatment only, and 19 who failed to respond to medical treatment received additional endovascular (n = 17) or surgical therapy (n = 2). Nine underwent IVC balloon angioplasty alone, 6 had angioplasty plus stents, and 2 had transjugular intrahepatic portosystemic shunts (TIPS) for hepatic vein lesions. One patient had a mesoatrial bypass; another had liver transplantation. Immediate response to the therapy was assessed with angiography and ultrasonography based on anatomic and/or hemodynamic correction or reduction of the lesion. Subsequent assessment of portal hypertension status was made with periodic clinical and laboratory evaluation (eg, ultrasonography, liver biopsy). RESULTS: Twenty-six patients had had IVC stenosis or occlusion by focal or segmental lesion. Two patients had hepatic vein outlet obstruction. There was no evidence of coagulopathy as the pathogenesis; all were related to membranous obstruction of the vena cava. Excellent immediate response to the endovascular therapy and subsequent relief of portal hypertension were achieved in 14 patients. Four patients had restenosis or progression of the residual lesion within 2 years; three responded to repeated stenting. Primary patency was 76.5%, and primary assisted patency was 94.1%. Two patients with TIPS and two with surgical therapy maintained excellent results. The medical treatment remained effective only in a limited group of 6 (21.4%) of the 28 patients. CONCLUSIONS: In BCS, both endovascular and surgical interventions provide excellent results and potentially halt liver parenchymal deterioration caused by portal hypertension. Liver transplantation remains the ultimate solution for advanced liver failure.